The unfolded protein response (UPR), which triggers cellular toxicity, is characteristic of prion disease, Alzheimer's disease and Parkinson's disease. This paper showed that an inhibitor of PERK (PRKR-like endoplasmic reticulum kinase), which is a mediator of the UPR pathway, prevented the development of prion disease in mice. Importantly, the orally available compound GSK2606414 also abolished established prion disease and restored the synthesis of synaptic proteins, although weight loss and hyperglycaemic side effects occurred. This study suggests that PERK could be targeted in neurodegenerative disorders that involve the UPR.
References
Moreno, J. A. et al. Oral treatment targeting the unfolded protein response prevents neurodegeneration and clinical disease in prion-infected mice. Sci. Transl. Med. 5, 206ra138 (2013)
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Harrison, C. A PERK for the therapy of prion disease. Nat Rev Drug Discov 12, 906 (2013). https://doi.org/10.1038/nrd4185
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DOI: https://doi.org/10.1038/nrd4185
